Interleukin‐1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST‐Segment–Elevation Myocardial Infarction

Background ST‐segment–elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin‐1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C‐reactive protein) levels during the first 14 days in patients with ST‐segment–elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo‐controlled, double‐blind, clinical trial in 99 patients with ST‐segment–elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39–120] versus 214 [interquartile range, 131–394] mg·day/L; P\u3c0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end‐systolic volume (median, 1.4 [interquartile range, −9.8 to 9.8] versus −3.9 [interquartile range, −15.4 to 1.4] mL; P=0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, −1.6% to 10.2%] versus 2.7% [interquartile range, −1.8% to 9.3%]; P=0.61) at 12 months. The incidence of death or new‐onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [P=0.046] and 0% versus 11.4% [P=0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P=0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P=0.016). Conclusions In patients presenting with ST‐segment–elevation myocardial infarction, interleukin‐1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299

CMB-S4

We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4

Strengthening integrated depression services within routine primary health care using the RE-AIM framework in South Africa.

Integration of mental health into routine primary health care (PHC) services in low-and middle-income countries is globally accepted to improve health outcomes of other conditions and narrow the mental health treatment gap. Yet implementation remains a challenge. The aim of this study was to identify implementation strategies that improve implementation outcomes of an evidence-based depression care collaborative implementation model integrated with routine PHC clinic services in South Africa. An iterative, quasi-experimental, observational implementation research design, incorporating the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework, was applied to evaluate implementation outcomes of a strengthened package of implementation strategies (stage two) compared with an initial evaluation of the model (stage one). The first stage package was implemented and evaluated in 10 PHC clinics and the second stage strengthened package in 19 PHC clinics (inclusive of the initial 10 clinics) in one resource-scarce district in the province of KwaZulu-Natal, South Africa. Diagnosed service users were more likely to be referred for counselling treatment in the second stage compared with stage one (OR 23.15, SE = 18.03, z = 4.04, 95%CI [5.03-106.49], p < .001). Training in and use of a validated, mandated mental health screening tool, including on-site educational outreach and technical support visits, was an important promoter of nurse-level diagnosis rates (OR 3.75, 95% CI [1.19, 11.80], p = 0.02). Nurses who perceived the integrated care model as acceptable were also more likely to successfully diagnose patients (OR 2.57, 95% CI [1.03-6.40], p = 0.043). Consistent availability of a clinic counsellor was associated with a greater probability of referral (OR 5.9, 95%CI [1.29-27.75], p = 0.022). Treatment uptake among referred service users remained a concern across both stages, with inconsistent co-located counselling services associated with poor uptake. The importance of implementation research for strengthening implementation strategies along the cascade of care for integrating depression care within routine PHC services is highlighted

Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure: Results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial)

An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF

Guidance document on the impact of water treatment processes on residues of active substances or their metabolites in water abstracted for the production of drinking water

Abstract This guidance document provides a tiered framework for risk assessors and facilitates risk managers in making decisions concerning the approval of active substances (AS) that are chemicals in plant protection products (PPPs) and biocidal products, and authorisation of the products. Based on the approaches presented in this document, a conclusion can be drawn on the impact of water treatment processes on residues of the AS or its metabolites in surface water and/or groundwater abstracted for the production of drinking water, i.e. the formation of transformation products (TPs). This guidance enables the identification of actual public health concerns from exposure to harmful compounds generated during the processing of water for the production of drinking water, and it focuses on water treatment methods commonly used in the European Union (EU). The tiered framework determines whether residues from PPP use or residues from biocidal product use can be present in water at water abstraction locations. Approaches, including experimental methods, are described that can be used to assess whether harmful TPs may form during water treatment and, if so, how to assess the impact of exposure to these water treatment TPs (tTPs) and other residues including environmental TPs (eTPs) on human and domesticated animal health through the consumption of TPs via drinking water. The types of studies or information that would be required are described while avoiding vertebrate testing as much as possible. The framework integrates the use of weight‐of‐evidence and, when possible alternative (new approach) methods to avoid as far as possible the need for additional testing